DNA-psoralen

FULL NAME: DNA-psoralen cross-link


DESCRIPTION:
These are photosensitizing furocoumarins or furanocoumarins with planar, tricyclic configurations. Upon photoreactivation with long-wavelength ultraviolet radiation, they form covalent adducts to pyrimidine bases on DNA. This results in DNA crosslinks, distortion and unwinding of DNA. Psoralens are found in many vegetables, like celery, fennel and parsnip and can cause contact phytophotodermatitis. However, they do not produce photodermatitis when taken orally. Interaction of psoralen with DNA to form 2 types of monoadducts (A+B) or a diadduct (C). The formation of the crosslink requires UV absorption events at each reaction. Interstrand cross-link (ICL) is a covalent modification of both strands of DNA, which prevents DNA strand separation during transcription and replication. Upon photoactivation 8-methoxypsoralen (8-MOP+UVA) alkylates both strands of DNA duplex at the 5,6-double bond of thymidines, generating monoadducts (MAs) and ICLs. It was thought that bulky DNA lesions such as MAs are eliminated only in the nucleotide excision repai (NER) pathway. Instead, non-bulky DNA lesions are substrates for DNA glycosylases and AP endonucleases which initiate the base excision repair (BER) pathway. BER might be involved in the removal of psoralen-DNA photoadducts. In human cells DNA glycosylase NEIL1 excises the MAs in duplex DNA, subsequently the apurinic/apyrimidinic endonuclease 1, APE1, removes the 3'-phosphate residue at single-strand break generated by NEIL1.

DAMAGE TYPE: crosslink


DNA DAMAGE SOURCE(S) (MAIN):
psoralen


DNA DAMAGE EFFECT(S) (MAIN):
cell cycle arrest
stalled replication fork


PATHWAYS:
base excision repair (BER)
nucleotide excision repair (NER)
prokaryotic (SOS) response


DNA repair protein(s) related to damage:
UvrC
UvrB
NEIL1


Last modification date: Dec. 14, 2011